The present invention relates to the preparation of carotenoids, particularly vitamin A. Although vitamin A is a relatively simple molecule, its construction has presented a formidable synthetic challenge. Prior art procedures for the preparation of vitamin A, as well as other carotenoids, involve extensive functionalization with concomitant stereochemical and stability problems. Other difficulties encountered with prior art syntheses involve coping with unstable reagents and intermediates. The foregoing factors have an adverse effect on the ultimate yield and steric purity of the final vitamin A product.
A very important consideration in the synthetic preparation of carotenoids and other natural products is the recognition of the fact that the isoprene C.sub.5 structure is the basic unit of such products. The biogenetic path of these products involves the incorporation of the C.sub.5 repeating unit into a large variety of open and ring structures. It is immediately apparent that isoprene represents an obvious choice as a starting material for carotenoid preparation. Attempts to synthesize natural products from isoprene normally require the functionalization of isoprene. Successful functionalizations of isoprene have involved the addition of anhydrous hydrochloride to isoprene yielding a mixture of prenyl chloride and isoprenyl chloride. This and other halogenation type reactions of isoprene are quite limited due to the difficulty of replacing the halogen substituents selectively with other functional groups. Even when the requisite functionalization has been accomplished, there still remain the problems described above.
The process of the instant invention avoids the problems of the prior art by employing .pi.-allyl complexes of transition metals and an isoprene derivative, the latter embodying the alcohol function which is to appear in the final product. The .pi.-allyl complex, described in greater detail hereinafter, is then coupled with a sulfone. The reaction product is further treated to obtain the desired carotene. In the case of vitamin A, the .pi.-allyl complex is coupled with a vinyl-.beta.-ionyl sulfone, prepared in accordance with Julia, U.S. Pat. No. 3,781,313.
In accordance with this invention, vitamin A and other carotenes are obtained in high yields and high steric purity while encountering none of the problems faced by prior art carotene syntheses.